Patent GB-1158331-A (GB)
Title: Delta<4,9,11>-Trienes of the 19-Nor-Androstane Series and Process for their manufacture
IPC: C07J75/00
Filed: 1966-07-25
Abstract: 1,158,331. #<SP>4 9 11</SP> - Androstatriene compounds. CIBA Ltd. 25 July, 1966 [30 July, 1965; 10 Sept., 1965], No. 33283/66. Heading C2U. 17 - Oxygenated #<SP>4</SP> <SP>9</SP> <SP>11</SP> - 3 - oxo - 19 - norandrostatrienes, claimed as novel when they contain a 7α-methyl substituent, are prepared by treating 17-oxygenated #<SP>5'10'</SP> <SP>9'11'</SP>-3-oxo-19- nor-androstadienes with one mol equivalent of an organic peracid, and treating the monoepoxides so obtained, or mixtures thereof, with a Lewis acid, if desired after treatment with an adsorbent containing silica or alumina. In the products free and functionally modified hydroxyl and/or oxo groups may be interconverted and/or a 17-oxo group may be reduced to a 17#-hydroxyl group (after temporary protection of the 3-oxo group, e.g. by conversion to the oxime) with or without the simultaneous introduction of a substituted or unsubstituted hydrocarbon radical into the 17α- position. The term " 17-oxygenated " refers to a free or functionally modified hydroxyl or oxo group, e.g. an esterified or etherified OH group or a ketalized oxo group. The treatment with an adsorbent converts the mono-epoxides into isomeric modified products, which are very probably 3 - oxo - 10 - hydroxy - #<SP>4</SP> 9'11'- or 3- oxo - 11α - hydroxy - #<SP>4</SP> <SP>9'10'</SP> - 19 - nor - androstadienes. 3 - Oxo - 7α - methyl - 17# - benzoyloxy - #<SP>5'10'</SP> <SP>9'11'</SP>-19-nor-androstadiene is prepared by Birch reduction of a 3-alkozy-7α-methyl-17#-hydroxy- #<SP>1 3</SP> <SP>5'10'</SP>-estratriene (prepared by LiAlH 4  reduction of the 17-one), hydrolysis of the thusformed 3 - alkoxy - 7α - methyl - 17# - hydroxy- #<SP>2</SP> <SP>5'10'</SP>-19-nor-androstadiene, bromination and dehydrobromination in pyridine of the thusformed 3 - oxo - 7α - methyl - 17# - hydroxy- #<SP>5'10'</SP> - 19 - nor - androstene to give 3 - oxo - 7α- methyl - 17# - hydroxy - #<SP>4</SP> 9 - 19 - nor - androstadiene, esterification to the 17-benzoate and conversion of this via a #<SP>3</SP> <SP>5'10'</SP> <SP>9'11'</SP>-enamine into the required product. 3-Oxo-7α,17α-dimethyl- 17# - hydroxy - #<SP>5'10'</SP> <SP> 9'11'</SP> - 19 - nor - androstadiene is prepared similarly from 3-methoxy-7α, 17α - dimethyl - 17# - hydroxy - #<SP>2</SP> <SP>5'10'</SP> - 19 - norandrostadiene (prepared by oxidizing 3-methoxy- 7α - methyl - 17# - hydroxy - #<SP>2</SP> <SP>5'10'</SP> - 19 - norandrostadiene to the corresponding 17-one and reacting this with CH 3 MgCl) via the corresponding #<SP>5'10'</SP> - 3 - one, 3 - oxo - 7α,17α - dimethyl- 17# - hydroxy - #<SP>4</SP> <SP>9</SP> - 19 - nor - androstadiene and 3 - pyrrolidino - 7α,17α - dimethyl - 17# - hydroxy- #<SP>3</SP> <SP>5'10'</SP> <SP>9'11'</SP> - 19 - nor - androstatriene. The corresponding 17α-ethynyl compounds are prepared similarly. 3,17 - Dioxo - 7α - methyl - #<SP>5'10'</SP> <SP>9'11'</SP> - 19-nor-androstadiene is prepared by ketalizing 3 - methoxy - 7α - methyl - 17 - oxo - #<SP>1</SP> <SP>8 5'10'</SP> <SP>9'11'</SP>- 19-nor-androstatetraene (prepared by methylation of the 3-ol) to give 3-methoxy-7α-methyl-17- ethylenedioxy - #<SP>1</SP> <SP>3 5'10'</SP> <SP>9'11'</SP> - 19 - nor - androstatetraene, epoxidizing this to the corresponding 9,11 - oxido - 1,3,5(10) - androstatriene, reducing this to 3 - methoxy - 7α - methyl - 11# - hydroxy- 17 - ethylenedioxy - #<SP>2</SP> <SP>5'10'</SP> - 19 - nor - androstadiene, converting this to 3,17-dioxo-7α-methyl- #<SP>4</SP> <SP>9</SP>-19-nor-androstadiene and converting this via a 3-enamine to'the required product. The novel steroids of the invention, which are stated to possess gestagenic, androgenic, anabolic and antigonadotropic action, may be made up into pharmaceutical compositions with suitable carriers.